Today two studies post positive data on the SARS-CoV-2 Omicron BA.4/BA.5 bivalent (two-strain) booster vaccine, with Pfizer/BioNTech announcing substantially greater immune response than the original vaccine in adults, and Centers for Disease Control and Prevention (CDC) researchers reporting similar rates of adverse events for both the Pfizer and Moderna bivalent COVID shots.
Antibody levels rise 13-fold in older group
Pfizer researchers drew sera from 114 study participants before and after the receipt of a 30-microgram mRNA Omicron BA.4/BA.5-adapted booster dose or a booster dose of the original monovalent (one-strain) vaccine, according to a company news release on updated data from its phase 2/3 multicenter clinical trial.
A subset of participants, evenly stratified by those with and without a previous infection, consisted of 38 adults 18 to 55 years old and 36 of those 56 and older. The team compared their results with those of 40 participants older than 55 years who had received an equivalent dose of the monovalent booster in an earlier study.
Bivalent vaccine recipients had received their third monovalent dose roughly 10 or 11 months earlier, and monovalent booster recipients had received their most recent dose about 7 months earlier. Prebooster SARS-CoV-2 antibody concentrations were similar.
One month after receipt of the bivalent booster, neutralizing antibody levels rose 13.2-fold (95% confidence interval [CI], 8.0 to 21.6) in adults older than 55 (geometric mean titer [GMT], 896) and 9.5-fold (95% CI, 6.7 to 13.6) higher (GMT, 606) in those aged 18 to 55. In comparison, the monovalent (single-strain) vaccine generated a 2.9-fold (95% CI, 2.1 to 3.9) increase in neutralizing antibody levels.
"Therefore, the Omicron BA.4/BA.5 neutralizing antibody titers were approximately 4-fold higher for the bivalent vaccine compared to the companies' original Covid-19 vaccine in individuals over 55 years of age," the release said.
Levels of antibodies against BA.4/BA.5 also rose significantly in all participants and to a greater extent in the previously infected recipients. Reports of adverse events were similar to those noted after receipt of the monovalent vaccine.
In the release, Pfizer CEO Albert Bourla, DVM, PhD, said the data "provide confidence in the adaptability of our mRNA platform and our ability to rapidly update the vaccine to match the most prevalent strains each season."
This fall, Pfizer's and Moderna's updated booster vaccine was authorized for Americans at least 5 years old and 18 years and older, respectively, who completed their primary vaccine series or received a monovalent booster dose at least 2 months earlier. In September, Pfizer started a phase 1/2/3 clinical trial on immune response, safety, and tolerability of different doses and dosing regimens of the updated vaccine in children aged 6 months to 11 years.
As safe as monovalent vaccine
Also today, in a study on the safety of the bivalent vaccine among Americans aged 12 years and older published in Morbidity and Mortality Weekly Report, researchers from the CDC and Food and Drug Administration discuss safety data from v-safe and the Vaccine Adverse Event Reporting System (VAERS) from the first 7 weeks after authorization.
From Aug 31 to Oct 23, 2022, about 14.4 Americans 12 years and older received a Pfizer bivalent booster dose, and 8.2 million aged 18 and older received Moderna's version. Of the recipients, 0.7% were aged 12 to 17 years, 32.4% were 18 to 49, 27.9% were 50 to 64, and 39.0% were 65 years and older.
A total of 211,959 people aged 12 years and older reported receiving a bivalent booster dose (58.0% Pfizer and 42.0% Moderna) to v-safe. The vast majority said that the booster dose was their fourth or fifth COVID-19 vaccine dose (45.4% and 50.2%, respectively).
Injection-site and systemic reactions were common in the week after receipt (60.8% and 54.8%, respectively) and decreased with age. The most common reactions were injection-site pain (range, 45.0% to 70.5%), fatigue (30.0% to 53.1%), headache (19.7% to 42.8%), muscle pain (20.3% to 41.3%), and fever (10.2% to 26.3%). From 10.6% to 19.8% of adults reported an inability to complete daily activities.
VAERS received 5,542 reports of adverse events after a bivalent booster dose; 95.5% of them were not serious. Among 251 reports of serious events, 5 involved myocarditis (inflammation of the heart muscle), 4 were pericarditis (inflammation of the membrane lining the heart), and 20 were COVID-19. Rates of myocarditis and pericarditis were similar to those observed after receipt of the primary series doses.
Those reporting myocarditis or pericarditis were 12 to 78 and 46 to 78 years old, respectively, but the conditions were most common among adolescent and young men. Thirty-six people died (median age, 71 years). In the four reports of death with sufficient information for review, the cause was listed as cardiac arrest, dementia, metastatic prostate cancer, and heart attack.
The most common nonserious reactions were headache (11.9%), fatigue (10.9%), fever (10.6%), pain (9.9%), and chills (8.7%). Adverse events related to administration errors (eg, incorrect vaccine formulation or dose, wrong product) were common, at 34.5%. Of the 877 reports of Pfizer vaccination errors and 1,037 of Moderna errors, 11.8% described an adverse event.
Few v-safe registrants (0.8%) reported seeking medical care, mainly via telehealth or clinic visit (0.3% each); 0.3% were hospitalized. Of the 45 registrants with information about hospitalization, 29 (64%) said it was unrelated to vaccination, and 13 (29%) completed a VAERS report.
"Healthcare providers and patients can be reassured that adverse events reported after a bivalent booster dose are consistent with those reported after monovalent doses," the researchers wrote. "Health impacts after COVID-19 vaccination are less frequent and less severe than those associated with COVID-19 illness."
